Engaging chromatin: PRC2 structure meets function

Chammas, Paul; Mocavini, Ivano; Croce, Luciano Di

doi:10.1038/s41416-019-0615-2

Cited by 104 publications

(88 citation statements)

References 174 publications

(308 reference statements)

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“…PcG and TrxG proteins not only control the transcriptional activity of the Hox complex genes, but also many other genes implicated in different aspects of development and differentiation. Moreover, disruption of the PcG or TrxG maintenance systems can result in developmental abnormalities and other pathologies [ 11 – 16 ].…”

Section: Introductionmentioning

confidence: 99%

Boundaries potentiate polycomb response element-mediated silencing

et al. 2021

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Background Epigenetic memory plays a critical role in the establishment and maintenance of cell identities in multicellular organisms. Polycomb and trithorax group (PcG and TrxG) proteins are responsible for epigenetic memory, and in flies, they are recruited to specialized DNA regulatory elements termed polycomb response elements (PREs). Previous transgene studies have shown that PREs can silence reporter genes outside of their normal context, often by pairing sensitive (PSS) mechanism; however, their silencing activity is non-autonomous and depends upon the surrounding chromatin context. It is not known why PRE activity depends on the local environment or what outside factors can induce silencing. Results Using an attP system in Drosophila, we find that the so-called neutral chromatin environments vary substantially in their ability to support the silencing activity of the well-characterized bxdPRE. In refractory chromosomal contexts, factors required for PcG-silencing are unable to gain access to the PRE. Silencing activity can be rescued by linking the bxdPRE to a boundary element (insulator). When placed next to the PRE, the boundaries induce an alteration in chromatin structure enabling factors critical for PcG silencing to gain access to the bxdPRE. When placed at a distance from the bxdPRE, boundaries induce PSS by bringing the bxdPREs on each homolog in close proximity. Conclusion This proof-of-concept study demonstrates that the repressing activity of PREs can be induced or enhanced by nearby boundary elements. Graphical abstract

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Section: Introductionmentioning

confidence: 99%

Boundaries potentiate polycomb response element-mediated silencing

et al. 2021

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“…The EED subunit of this complex binds the H3K27me3 mark to allosterically activate the EZH2 catalytic subunit, thereby propagating the mark to neighboring nucleosomes (Margueron et al, 2009;Oksuz et al, 2018). Our current understanding of polycomb proteins is evolving at a fast pace, and is well discussed in recent publications (Cheutin and Cavalli, 2019;Laugesen et al, 2019;van Mierlo et al, 2019;Yu et al, 2019;Chammas et al, 2020).…”

Section: Histone Variants and Post-translational Modificationsmentioning

confidence: 99%

Interactions With Histone H3 & Tools to Study Them

Scott

Campos

2020

Front. Cell Dev. Biol.

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Histones are an integral part of chromatin and thereby influence its structure, dynamics, and functions. The effects of histone variants, posttranslational modifications, and binding proteins is therefore of great interest. From the moment that they are deposited on chromatin, nucleosomal histones undergo dynamic changes in function of the cell cycle, and as DNA is transcribed and replicated. In the process, histones are not only modified and bound by various proteins, but also shuffled, evicted, or replaced. Technologies and tools to study such dynamic events continue to evolve and better our understanding of chromatin and of histone proteins proper. Here, we provide an overview of H3.1 and H3.3 histone dynamics throughout the cell cycle, while highlighting some of the tools used to study their protein-protein interactions. We specifically discuss how histones are chaperoned, modified, and bound by various proteins at different stages of the cell cycle. Established and select emerging technologies that furthered (or have a high potential of furthering) our understanding of the dynamic histone-protein interactions are emphasized. This includes experimental tools to investigate spatiotemporal changes on chromatin, the role of histone chaperones, histone posttranslational modifications, and histone-binding effector proteins.

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“…The striking changes observed by Long et al after RNase A treatment point toward a fundamental role of RNA in shaping PRC2 occupancy and call into question the relevance of all previously described PRC2-chromatin interactions (that is, PCL binding to unmethylated CpG dinucleotides and H3K36me3; Jarid2 binding to H2AK119ub; and H2K27me3-mediated PRC2 activation) 2,3 . The so-called 'junk-mail' model might provide a comprehensive solution 6 : RNA could be the driver of broad, non-specific PRC2 recruitment to chromatin, and only regions decorated with suitable chromatin modifications would elicit productive PRC2 engagement, thus resulting in local H3K27me3 deposition.…”

Section: A Complicated Way To Silencementioning

confidence: 99%

“…PRC2 localization in mammalian cells correlates with certain chromatin features, including unmethylated CpGs and ubiquitinated histone H2A K119 (H2AK119ub), a mark that is in turn deposited by PRC1 (refs. 2,3 ; Fig. 1).…”

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confidence: 97%